Rheumatoid Arthritis Flashcards
What type of disease is RA
Autoimmune
Where does RA affect
Synovial joints
Hands feet knees hips
What are the 4 phases of pathophysiology for RA
INITIATOR PHASE- Injury, infection etc.
antigen presenting cells now seen as non-self
INFLAMMATORY PHASE- self antigens presented, clonal expansion of T and B cells
Insufficiently controlled by Treg Cells
SELF PERPETUATING PHASE- Inflammatory damage in synovium means self antigens are exposed causing immune response against cartilage and immune cells to gather.
DESTRUCTION PHASE- synovial fibroblasts and osteoclasts activated by cytokines (TNF, IL-6) causing destruction of bone and cartilage.
What do B-cells do in RA
Produce autoantibodies which bind to macrophages in synovium and sustain inflammation
What does rheumatoid Factor do
Directed against antigens usually present outside of joint
What might joint destruction be caused by?
CD4 T-cell cytokine causes RANK ligand promoting osteoclasts to resorb bone
How do you diagnose Rheumatoid arthritis?
Anti-CCP levels
squeeze test
What do T-cells do in Rheumatoid arthritis
Potentially activate monocytes, macrophages and synovial fibroblasts -> produces TNF-a, IL-1, IL-6-> induce production on matrix metalloproteases (MMP’s) which degrade cartilage
What are the signs and symptoms of RA?
Fever, weakness
Symmetrical inflammation
Progressive loss of function
Weight loss and fatigue
What are patients with RA and increased risk of?
CV risk
Infection
Respiratory disease
osteoporosis
Malignancy
depression
What is tested in blood tests for RA?
Usually anti-CCP (anti-cyclic citrullinated peptide)
Rheumatoid factor (RF)
C-reactive protein (CRP)
Erythrocyte sedimentation rate (ESR)
What tests are needed for a diagnosis?
Complete history taking-
Morning stiffness for more than 30mins
Stiff after resting
Family history and lifestyle
Clinical presentation-
Symmetrical effects of synovial joints
Symptoms worsen
Investigations-
Inflammatory markers
Haematological and immunological parameters
Radiological Investigations
What does NICE say for diagnosis of RA
Clinical examination shows synovitis
Determine RF and Anti-CCP antibodies (if -ve for RF)
X-ray hands and feet
What does DAS28 consider for RA? What is it?
Measure disease activity
1- No. of swollen joints (out of 28)
2- No. of tender joints
3- Measure ESR or CRP
4- Global assessment of health
more than 5.1 = active
less than 3.2 = low activity
less than 2.6 = remission!
What treatments are available for RA?
NSAID’s
Glucocorticoids
DMARD’s - methotrexate, sulfasalazine, leflunomide
Biologics - Anti-TNF
- IL-6 receptor inhibitor (tocilizumab)
- Anti B-cell (rituximab)
- Antibody blocking T-cell activation (Abatacept)
- Il-1 receptor inhibitor (anakinra)
Targeted tDMARD- JAK inhibitors: nibs
tofacitinib
baricitinib
